Glycolonitrile (HOCH2CN; CAS Registry Number 107-16-4) is an α-hydroxynitrile that can be enzymatically converted to glycolic acid using a catalyst having nitrilase activity or a combination of nitrile hydratase and amidase activities. Glycolic acid (HOCH2CO2H; CAS Registry Number is 79-14-1) is the simplest member of the α-hydroxy acid family of carboxylic acids. Its properties make it ideal for a broad spectrum of consumer and industrial applications, including use in water well rehabilitation, the leather industry, the oil and gas industry, the laundry and textile industry, and as a component in personal care products like skin creams. Glycolic acid also is a principle ingredient for cleaners in a variety of industries (dairy and food processing equipment cleaners, household and institutional cleaners, industrial cleaners [for transportation equipment, masonry, printed circuit boards, stainless steel boiler and process equipment, cooling tower/heat exchangers], and metals processing [for metal pickling, copper brightening, etching, electroplating, electropolishing]).
Glycolonitrile is also a versatile intermediate in the preparation of aminonitriles, which are, in turn, useful in preparing aminocarboxylic acid compounds. For example, U.S. Pat. No. 5,208,363 discloses the use of glycolonitrile in the preparation of aminonitrile precursors for the production of ethylenediaminetetraacetic acid (EDTA), and U.S. Pat. No. 5,817,613 describes the use of glycolonitrile in the synthesis of 2-hydroxyethyl iminodiacetic acid (HEIDA). EDTA and HEIDA are useful as chelating agents as components of detergent compositions. FR1575475 describes the use of glycolonitrile in the synthesis of alkali metal salts of nitrilotriacetic acid. In addition, glycolonitrile can be used as a precursor to glycinonitrile, which can be converted to glycine as disclosed in US2003/0040085. Glycine is widely used as an additive in processed meats and beverages, and as a raw material for the commercially important herbicide, N-(phosphonomethyl)glycine, also known by its common name glyphosate, as described in U.S. Pat. No. 6,759,549.
Microbial catalysts can hydrolyze a nitrile (e.g., glycolonitrile) directly to the corresponding carboxylic acids (e.g., glycolic acid) using a nitrilase (EC 3.5.5.7), where there is no intermediate production of the corresponding amide (Equation 1), or by a combination of nitrile hydratase (EC 4.2.1.84) and amidase (EC 3.5.1.4) enzymes, where a nitrile hydratase (NHase) initially converts a nitrile to an amide, and then the amide is subsequently converted by the amidase to the corresponding carboxylic acid (Equation 2):

Enzymatic synthesis of glycolic acid requires a substantially pure form of glycolonitrile. Methods to synthesize glycolonitrile by reacting aqueous solutions of formaldehyde and hydrogen cyanide have previously been reported (U.S. Pat. No. 2,175,805; U.S. Pat. No. 2,890,238; and U.S. Pat. No. 5,187,301; Equation 3).HCN+HCHO→HOCH2CN  (3)
Concentrated aqueous solutions of formaldehyde (e.g., 37 wt % solutions commercially known as formalin) typically are comprised of free formaldehyde and various oligomers of formaldehyde (for example, paraformaldehyde and trixoxymethylene). The presence of formaldehyde oligomers can influence overall conversion to glycolonitrile. Hence, a method to pre-treat the formaldehyde that transforms formaldehyde oligomers to more free formaldehyde in the feed stream prior to reacting with hydrogen cyanide should increase the yield of glycolonitrile and should decrease the conversion of unwanted secondary products produced from the oligomers.
Jacobson (U.S. Pat. No. 2,175,805) discloses a method of obtaining pure glycolonitrile by the reaction of hydrogen cyanide and formaldehyde in the presence of an acidic compound followed by distillation at subatmospheric pressure (vacuum distillation step conducted at about 125° C.). The reactants are preferably mixed “in the cold” (i.e., below 26° C. to maintain the hydrogen cyanide in liquid form). Also described in U.S. Pat. No. 2,175,805 is the observation that 1) glycolonitrile decomposes at ambient temperature, and 2) glycolonitrile contacted with bases decomposes violently within hours at ambient temperature. Jacobson does not disclose pre-treatment of the concentrated aqueous formaldehyde feed prior to reacting with hydrogen cyanide.
Sexton (U.S. Pat. No. 2,890,238) discloses a method of preparing glycolonitrile in which formaldehyde is fed into an aqueous solution of HCN. The reaction is run “with efficient reflux or a closed pressure system, with the reaction allowed to go as high as 100° C.” However, as described in Jacobson, glycolonitrile decomposes at room temperature. A reaction run at temperatures as high as 100° C. would be expected to result in an increase in the decomposition of the glycolonitrile. Similar to Jacobson, Sexton does not describe a method to pre-treat the formaldehyde prior to reacting with hydrogen cyanide.
Cullen etal. (U.S. Pat. No. 5,187,301) discloses a method for making iminodiacetonitrile from glycolonitrile. This reference describes how glycolonitrile can be formed in a process (either batch or continuous) by maintaining the pH of the formaldehyde above about 3, preferably in the range of about 5-7, most preferably about 5.5, with suitable acids and bases. The formaldehyde is then reacted with hydrogen cyanide in a temperature range of about 20 to 80° C., preferably about 30° C., to form glycolonitrile. However, as shown in the present examples, a reaction run within the conditions specified in Cullen et al. results in a significant amount of unreacted free formaldehyde after 2 hours of reaction time.
All of the above mentioned methods produce a purity of glycolonitrile that typically requires extensive processing steps, such as distillative purification, to remove some of the secondary products (impurities). Many of the impurities found in glycolonitrile, such as unreacted formaldehyde, have been reported to interfere with the enzymatic conversion to glycolic acid by inactivating the enzyme catalyst (U.S. Pat. No. 5,756,306; U.S. Pat. No. 5,508,181; and U.S. Pat. No. 6,037,155; hereby incorporated in their entirety by reference).
The problem to be solved is the lack of a method to produce glycolonitrile by reacting formaldehyde and hydrogen cyanide under conditions that produce a substantially pure reaction product. Specifically, a method is lacking that reduces the amount of unreacted formaldehyde (one of the impurities associated with enzyme inactivation when converting glycolonitrile to glycolic acid), and minimizes the number of post-reaction purification steps.